MoD 3 Acute Inflammation

Question 1

What is acute inflammation?

Answer 1

Response of living tissue to injury, initiated to limit tissue damage.
Innate, immediate and early, stereotyped, short duration (mins/hrs/few days)

Question 2

What can cause acute inflammation?

Answer 2

Microbial infections (e.g pyogenic organisms)
Hypersensitivity reactions (acute phase)
Physical agents
Chemicals
Tissue necrosis

Question 3

What are the main clinical signs of acute inflammation?

Answer 3

RUBOR-redness
TUMOR-swelling
CALOR-heat
DOLOR-pain
& loss of function

Question 4

What changes in tissues occur?

Answer 4

Changes in blood flow
Exudation of fluid into tissues
Infiltration of inflammatory cells

Question 5

What are the changes in blood flow?

Answer 5

transient vasoconstriction of arterioles (few secs)
Vasodilatation fo arterioles then capillaries -> inc blood flow(heat then redness)
Increased permeability of blood vessels ->protein rich exudation and slowing circulation (swelling)
inc RBC conc in small vessel and increased viscosity can lead to stasis

Question 6

What are the microscopic steps in acute inflammation?

Answer 6

1. Vasodilation
2. Gaps form in endothelium
3. Exudation
4. Margination and emigration- neutrophils adhere to swollen endothelial cells and migrate through vessel basement membrane
5. Marcrophages and lymphocytes migrate in a similar way to neutrophils

Question 7

What chemical mediators cause vasodilation?

Answer 7

Histamine, prostaglandins, C3a, C5a

Question 8

What chemical mediators cause increased vascular permeability?

Answer 8

Histamine, prostaglandins, Kinins

Question 9

What chemical mediators cause emigration of leukocytes?

Answer 9

Leukotrienes, IL-8, C5a

Question 10

Discuss the actions of neutrophils

Answer 10

phagocytose organisms by making contact, recognising and internalising them then fusing with lysosomes to destroy the contents.
Neutrophils move to the site of injury by chemotaxis.
Activated neutrophils may also release toxic metabolites and enzymes causing damage to host tissue

Question 11

What are the systemic consequences of acute inflammation?

Answer 11

Acute phase response
fever
leukocytosis

Question 12

What occurs in acute phase response?

Answer 12

Decreased appetite, raised heart rate, altered sleep patterns and changes in plasma conc of acute phase proteins e.g C-Reactive Proteins (CRP), fibrinogen and a1-antitrypsin
Spread of microorganisms and toxins may lead to shock, a clinical syndrome of circulatory failure

Question 13

What endogenous pyrogens are produced?

Answer 13

IL-1, TNFalpha, and prostaglandin

Question 14

What is fluid flow across vessel walls determined by?

Answer 14

Balance between hydrostatic and colloid osmotic pressure in the plasma and interstitial fluid.
Increasing hydrostatic inside or colloid osmotic pressure outside increases flow out of the vessel

Question 15

What may happen after the development of acute inflammation?

Answer 15

Complete resolution
Continued acute inflammation with chronic inflammation(abscess)
Chronic inflammation and fibrous repair, probably with tissue regeneration
Death

Question 16

How does resolution occur?

Answer 16

All mediators of acute inflammation have short half lives and may be inactivated by degradation, dilution in exudate or inhibition
Gradually all changes reverse and vascular changes stop. Neutrophils no longer marginate, vessel permeability returns to normal and exudate drains via lymphatics

Question 17

When is complete resolution not possible?

Answer 17

If the collagen framework/tissue architecture has been destroyed

Question 18

Describe some complications of acute inflammation?

Answer 18

Swelling- Blockage of tubes e.g. bile duct, intestine
Exudate-Compression e.g cardiac tamponade, serositis
Loss of fluid e.g burns
Pain and loss of function- especially if prolonged

Question 19

Describe skin blisters

Answer 19

Caused by heat, sunlight, chemicals
pain and profuse exudate
Collection of fluid strips of overlying epithelium
Relatively few inflammatory cells so exudate clear
Resolution or scarring

Question 20

Describe Abscesses

Answer 20

Solid tissues
Inflammatory exudate forces tissue apart
Liquefactive necrosis in centre
May cause high pressure and so pain
May cause tissue damage and squash adjacent structures

Question 21

Describe Pericarditis

Answer 21

Inflammation of serous cavity

Pericardium becomes inflamed and increases pressure on heart

Question 22

Give examples of inherited disorders of the acute inflammatory process

Answer 22

alpha1 anti-trypsin deficiency
Inherited complement deficiencies e.g Hereditary Angio-Oedema
Defects in neutrophil function e.g Chronic Granulomatous Disease
Defects in neutrophil number

Question 23

What is Hereditary Angio-Oedema?

Answer 23

Caused by a deficiency of C1 inhibitor so C1 cleaves C2 and C4 to form C3
The C1 inhibitor usually inhibits Bradykinin too and uninhibited bradykinin increases endothelial permeability causing oedema.

Question 24

How is Hereditary Angio-Oedema treated?

Answer 24

C1 inhibitor infusion or fresh frozen plasma

Question 25

What is alpha1 anti-trypsin deficiency?

Answer 25

alpha1 anti-trypsin inhibits elastase

Without inhibition elastase breaks down lung and liver tissue causing emphysema and liver sclerosis

Question 26

What is Chronic Granulomatous Disease?

Answer 26

Recessive sex linked
Immune phagocytes can’t form ROS
Cant kill some bacteria without ROS
Granulomas form in attempt to contain the bacteria